ShirleyP wrote:I also carry rs 2075650 (GG) on TOMM40 which increases the risk for late onset Alzheimer's 4x more than usual.
The authors estimated that people with two ApoE-ε4 copies (i.e. presumably indicated by having either the rs4420638(G;G) or rs429358(C;C)genotypes) have a 25-fold increased risk for developing the disease compared to Apo-ε3/Apo-ε3 carriers. https://www.snpedia.com/index.php/APOE
Hi ShirleyP and notmygenes56,
Looks like you are both interested in the world of SNPs, which are the subject of considerable study by researchers all around the world. I think it's important to realize that finding that SNPs are associated with a disease does not necessarily mean that they cause that disease, or that they multiply the risk of other alleles which are associated with a disease.
The reference that you quoted from snpedia
, that claims a 25-fold increased risk of developing Alzheimer's disease (AD) for Apoe 4/4 vs. Apoe 3/3 is from January 2007, Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.
In genetics research that data is like having a 2007 cell phone. A "25-fold increased risk" would mean that If people with ApoE 4/4 had a 100% chance of getting AD (which they don't), then lucky Apoe 3/3's have only a 4% chance. If, as is more likely, people with Apoe4/4 have a 30-55% risk of EITHER mild cognitive impairment or Alzheimers by age 85, then that would mean someone with Apoe 3/3 has a 1.2-2.2% chance of having Alzheimers.
The truth is that somewhere between a large minority (45%) and a majority (70%) of people between the ages of 60 and 75 now alive with ApoE 4/4 will NOT get either MCI or AD before they die from something else. And about 10-15% of people with Apoe 3/3 will get MCI or AD. The results are almost certainly going to be better for younger people who will have the benefit of lifestyle interventions and possibly preventive medications. APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
As for the risk that you Shirley, might have an added 4x the risk of AD from that TOMM 40 GG SNP:
Here's the summary of meta-analysis published in 2015 that looked at the association between the TOMM 40 GG SNP and AD. After studying 4290 cases 0f AD and 5556 healthy individuals, the most they can say is that the results are "inconsistent" and there "may" be an association. That doesn't even prove an association with TOMM 40 and AD, much less that it adds to the risk of ApoE 3/4.
The association between the TOMM40 rs2075650 polymorphism and Alzheimer disease was examined by overall odds ratio (OR) with a 95 % confidence interval (CI). We used different genetic model analysis, sensitivity analysis, and assessments of bias in our meta-analysis.
RESULTS: The pooled analysis showed the inconsistent results that TOMM40 rs2075650 polymorphism was associated with Alzheimer disease in European and Korean population in all genetic models, but there was no significant association between the TOMM40 rs2075650 polymorphism and Alzheimer disease risk in Chinese population.
CONCLUSION: We conclude that rs2075650 in TOMM40 gene may increase the risk of Alzheimer disease.
[Emphasis added.]Meta-analysis of the rs2075650 polymorphism and risk of Alzheimer disease.
A "rule" I try to follow in reading articles on individual SNPs and risk: Don't believe studies of small groups of people, or people in one geographic area. (Even if I'm glad that young men in Denmark with a SNP I carry do well on Wellbutrin for anxiety.) Instead look for recent articles and meta-analyses.
Don't sweat the big risk statistics: no one can tell you what YOUR risk is based on people who may have been misdiagnosed as having AD and were born around the time of your grandparents. Focus on making healthy choices in food, exercise, sleep and stress reduction and you will reduce many of the risk factors without reading any articles.